The biological significance of antibodies to nucleic acids and nucleoproteins is being investigated with major emphasis on antibodies to the Sm antigen which appear spontaneously in patients with systemic lupus erythematosus and in murine models for this disease. Our previous studies have shown that antibodies to DNA and RNA are regulated by the thymus and other lymphoid organs as well as by sex steroid hormones. These studies are continuing using monoclonal antibodies to lymphocyte surface antigens and the fluorescence activated cell sorter. In addition, new studies are proposed to investigate the immunoregulation of the spontaneous and induced antibody response to Sm antigen in MRL/1pr mice and other strains bearing the 1pr gene. We will prepare antiidiotypic antisera against monoclonal anti-Sm antibodies produced by several hybridomas available in our laboratory. These antiidiotypic antisera will be used as reagents to explore cell surface receptors and to search for cross reactive idiotypes. Specific helper and suppressor T cell subpopulations will be investigated in an in vitro system measuring anti-Sm antibody and in nude mice which will be used as an in vivo culture system. Clones of immunoregulatory T cells specific for the Sm system will be developed. Ricin toxin will be conjugated to the Sm antigen in an attempt to eliminate specific B cells. The goal of this grant is to restore immunologic control and suppress autoantibody formation in lupus mice and ultimately in patients.